{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T04:29:39Z","timestamp":1772684979828,"version":"3.50.1"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,6,2]],"date-time":"2023-06-02T00:00:00Z","timestamp":1685664000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Obsessive\u2013compulsive disorder (OCD), characterized by the presence of obsessions and\/or compulsions, is often difficult to diagnose and treat in routine clinical practice. The candidate circulating biomarkers and primary metabolic pathway alteration of plasma in OCD remain poorly understood.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We recruited 32 drug-na\u00efve patients with severe OCD and 32 compared healthy controls and applied the untargeted metabolomics approach by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF\/MS) to assess their circulating metabolic profiles. Both univariate and multivariate analyses were then utilized to filtrate differential metabolites between patients and healthy controls, and weighted Correlation Network Analysis (WGCNA) was utilized to screen out hub metabolites.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 929 metabolites were identified, including 34 differential metabolites and 51 hub metabolites, with an overlap of 13 metabolites. Notably, the following enrichment analyses underlined the importance of unsaturated fatty acids and tryptophan metabolism alterations in OCD. Metabolites of these pathways in plasma appeared to be promising biomarkers, such as Docosapentaenoic acid and 5-Hydroxytryptophan, which may be biomarkers for OCD identification and prediction of sertraline treatment outcome, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings revealed alterations in the circulating metabolome and the potential utility of plasma metabolites as promising biomarkers in OCD.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnins.2023.1148971","type":"journal-article","created":{"date-parts":[[2023,6,2]],"date-time":"2023-06-02T09:17:01Z","timestamp":1685697421000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Untargeted metabolomics analysis in drug-na\u00efve patients with severe obsessive\u2013compulsive disorder"],"prefix":"10.3389","volume":"17","author":[{"given":"Zheqin","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian","family":"Gao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liangjun","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zifeng","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susu","family":"Yan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weidi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongdong","family":"Shi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhen","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,6,2]]},"reference":[{"key":"ref1","volume-title":"Diagnostic and statistical manual of mental disorders","year":"2013"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1038\/s41592-021-01197-1","article-title":"Mass spectrometry-based metabolomics: a guide for annotation, quantification and best reporting practices","volume":"18","author":"Alseekh","year":"2021","journal-title":"Nat. Methods"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"833","DOI":"10.1001\/jamapsychiatry.2017.1567","article-title":"Inflammation in the Neurocircuitry of obsessive-compulsive disorder","volume":"74","author":"Attwells","year":"2017","journal-title":"JAMA Psychiat."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"588","DOI":"10.1207\/s15327752jpa6703_13","article-title":"Comparison of Beck depression inventories -IA and -II in psychiatric outpatients","volume":"67","author":"Beck","year":"1996","journal-title":"J. Pers. Assess."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1001\/archpsyc.1961.01710120031004","article-title":"Beck depression inventory (BDI)","volume":"4","author":"Beck","year":"1961","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1016\/0165-1781(91)90067-Y","article-title":"Plasma catecholamines and their metabolites in obsessive-compulsive disorder","volume":"37","author":"Benkelfat","year":"1991","journal-title":"Psychiatry Res."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"853","DOI":"10.1016\/j.biopsych.2005.08.023","article-title":"Lack of effects on core obsessive-compulsive symptoms of tryptophan depletion during symptom provocation in remitted obsessive-compulsive disorder patients","volume":"59","author":"Berney","year":"2006","journal-title":"Biol. Psychiatry"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"2489","DOI":"10.1038\/npp.2009.77","article-title":"Anti-brain autoantibodies and altered excitatory neurotransmitters in obsessive-compulsive disorder","volume":"34","author":"Bhattacharyya","year":"2009","journal-title":"Neuropsychopharmacology"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"67","DOI":"10.3390\/jcm5080067","article-title":"Supplementation with Omega-3 fatty acids in psychiatric disorders: a review of literature data","volume":"5","author":"Bozzatello","year":"2016","journal-title":"J. Clin. Med."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.biopsych.2012.06.023","article-title":"A critical review of magnetic resonance spectroscopy studies of obsessive-compulsive disorder","volume":"73","author":"Brennan","year":"2013","journal-title":"Biol. Psychiatry"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1016\/j.ejphar.2018.08.009","article-title":"L-tryptophan administration and increase in cerebral serotonin levels: systematic review","volume":"836","author":"Carneiro","year":"2018","journal-title":"Eur. J. Pharmacol."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1016\/0165-1781(92)90025-X","article-title":"Melatonin and cortisol secretion in patients with primary obsessive-compulsive disorder","volume":"44","author":"Catapano","year":"1992","journal-title":"Psychiatry Res."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"1735","DOI":"10.1038\/sj.npp.1300733","article-title":"Glutamatergic dysfunction in OCD","volume":"30","author":"Chakrabarty","year":"2005","journal-title":"Neuropsychopharmacology"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"5342","DOI":"10.1021\/acs.analchem.6b05152","article-title":"Influences of normalization method on biomarker discovery in gas chromatography\u2013mass spectrometry-based untargeted metabolomics: what should be considered?","volume":"89","author":"Chen","year":"2017","journal-title":"Anal. Chem."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1016\/j.sleep.2020.03.021","article-title":"Sleep duration and timing in obsessive-compulsive disorder (OCD): evidence for circadian phase delay","volume":"72","author":"Coles","year":"2020","journal-title":"Sleep Med."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"1539","DOI":"10.1038\/sj.npp.1300752","article-title":"Platelet serotonergic markers as endophenotypes for obsessive-compulsive disorder","volume":"30","author":"Delorme","year":"2005","journal-title":"Neuropsychopharmacology"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1037\/1040-3590.14.4.485","article-title":"The obsessive-compulsive inventory: development and validation of a short version","volume":"14","author":"Foa","year":"2002","journal-title":"Psychol. Assess."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1016\/j.pnpbp.2005.11.001","article-title":"The descriptive epidemiology of obsessive-compulsive disorder","volume":"30","author":"Fontenelle","year":"2006","journal-title":"Prog. Neuro-Psychopharmacol. Biol. Psychiatry"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"2217","DOI":"10.1093\/advances\/nmac084","article-title":"Unsaturated fatty acids in mental disorders: an umbrella review of meta-analyses","volume":"13","author":"Gao","year":"2022","journal-title":"Adv. Nutr."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1007\/s11920-019-1062-8","article-title":"Obsessive-compulsive disorder: autoimmunity and Neuroinflammation","volume":"21","author":"Gerentes","year":"2019","journal-title":"Curr. Psychiatry Rep."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1016\/j.drudis.2007.12.009","article-title":"Serotoninergic mechanisms in the treatment of obsessive-compulsive disorder","volume":"13","author":"Goddard","year":"2008","journal-title":"Drug Discov. Today"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"1006","DOI":"10.1001\/archpsyc.1989.01810110048007","article-title":"The Yale-Brown obsessive compulsive scale. I. Development, use, and reliability","volume":"46","author":"Goodman","year":"1989","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1177\/070674370304800308","article-title":"Essential fatty acids and the brain","volume":"48","author":"Haag","year":"2003","journal-title":"Can. J. Psychiatr."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1186\/s13059-017-1215-1","article-title":"Multi-omics approaches to disease","volume":"18","author":"Hasin","year":"2017","journal-title":"Genome Biol."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1016\/0165-1781(92)90081-D","article-title":"Effects of fenfluramine on plasma HVA in OCD","volume":"42","author":"Hollander","year":"1992","journal-title":"Psychiatry Res."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"1615","DOI":"10.1177\/0269881117736916","article-title":"Effects of tryptophan depletion on selective serotonin reuptake inhibitor-remitted patients with obsessive compulsive disorder","volume":"31","author":"Hood","year":"2017","journal-title":"J. Psychopharmacol."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.plipres.2013.10.002","article-title":"Long-chain polyunsaturated fatty acids (LCPUFA) from genesis to senescence: the influence of LCPUFA on neural development, aging, and neurodegeneration","volume":"53","author":"Janssen","year":"2014","journal-title":"Prog. Lipid Res."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"sbac130","DOI":"10.1093\/schbul\/sbac130","article-title":"Association between human blood metabolome and the risk of psychiatric disorders","volume":"49","author":"Jia","year":"2022","journal-title":"Schizophr. Bull."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1093\/nar\/28.1.27","article-title":"KEGG: Kyoto encyclopedia of genes and genomes","volume":"28","author":"Kanehisa","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1586\/ern.09.148","article-title":"Role of dopamine in the pathophysiology and treatment of obsessive-compulsive disorder","volume":"10","author":"Koo","year":"2010","journal-title":"Expert. Rev. Neurother."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1159\/000115778","article-title":"Effects of tryptophan depletion on cognitive functioning, obsessive-compulsive symptoms and mood in obsessive-compulsive disorder: preliminary results","volume":"56","author":"K\u00fclz","year":"2007","journal-title":"Neuropsychobiology"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1186\/1471-2105-9-559","article-title":"WGCNA: an R package for weighted correlation network analysis","volume":"9","author":"Langfelder","year":"2008","journal-title":"BMC Bioinformatics"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.pscychresns.2011.01.017","article-title":"Proton magnetic resonance spectroscopy in pediatric obsessive-compulsive disorder: longitudinal study before and after treatment","volume":"201","author":"L\u00e1zaro","year":"2012","journal-title":"Psychiatry Res."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1038\/sj.npp.1380241","article-title":"Cerebrospinal fluid biogenic amines in obsessive compulsive disorder, Tourette\u2019s syndrome, and healthy controls","volume":"12","author":"Leckman","year":"1995","journal-title":"Neuropsychopharmacology"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/0165-1781(92)90043-3","article-title":"Plasma tryptophan levels and plasma tryptophan\/neutral amino acids ratio in patients with mood disorder, patients with obsessive-compulsive disorder, and normal subjects","volume":"44","author":"Lucca","year":"1992","journal-title":"Psychiatry Res."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1111\/acps.13026","article-title":"Oxidative and nitrosative stress markers in obsessive-compulsive disorder: a systematic review and meta-analysis","volume":"139","author":"Maia","year":"2019","journal-title":"Acta Psychiatr. Scand."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1176\/appi.ajp.162.2.228","article-title":"A multidimensional model of obsessive-compulsive disorder","volume":"162","author":"Mataix-Cols","year":"2005","journal-title":"Am. J. Psychiatry"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"874","DOI":"10.1016\/S0006-3223(97)00512-X","article-title":"Plasma melatonin and cortisol in patients with obsessive-compulsive disorder: relationship with axillary temperature, physical activity, and clinical symptoms","volume":"44","author":"Millet","year":"1998","journal-title":"Biol. Psychiatry"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1186\/s12991-021-00354-2","article-title":"Malondialdehyde concentrations in obsessive-compulsive disorder: a systematic review and meta-analysis","volume":"20","author":"Mohammadi","year":"2021","journal-title":"Ann. General Psychiatry"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1016\/j.beth.2019.12.006","article-title":"Delayed bedtimes are associated with more severe obsessive-compulsive symptoms in intensive residential treatment","volume":"51","author":"Nota","year":"2020","journal-title":"Behav. Ther."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1016\/j.pnpbp.2005.11.028","article-title":"Treatment-refractory obsessive-compulsive disorder: methodological issues, operational definitions and therapeutic lines","volume":"30","author":"Pallanti","year":"2006","journal-title":"Prog. Neuro-Psychopharmacol. Biol. Psychiatry"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1038\/nrn3746","article-title":"Obsessive\u2013compulsive disorder: an integrative genetic and neurobiological perspective","volume":"15","author":"Pauls","year":"2014","journal-title":"Nat. Rev. Neurosci."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1016\/j.pharmthera.2011.09.006","article-title":"Glutamate abnormalities in obsessive compulsive disorder: neurobiology, pathophysiology, and treatment","volume":"132","author":"Pittenger","year":"2011","journal-title":"Pharmacol. Ther."},{"key":"ref44","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1038\/s41573-019-0016-5","article-title":"Tryptophan metabolism as a common therapeutic target in cancer, neurodegeneration and beyond","volume":"18","author":"Platten","year":"2019","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref45","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1038\/s41580-019-0108-4","article-title":"Identification of bioactive metabolites using activity metabolomics","volume":"20","author":"Rinschen","year":"2019","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref46","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1016\/j.psychres.2011.01.019","article-title":"A preliminary randomized double-blind clinical trial on the efficacy of celecoxib as an adjunct in the treatment of obsessive-compulsive disorder","volume":"189","author":"Sayyah","year":"2011","journal-title":"Psychiatry Res."},{"key":"ref47","doi-asserted-by":"publisher","first-page":"2565","DOI":"10.3389\/fimmu.2019.02565","article-title":"Tryptophan metabolism in Inflammaging: from biomarker to therapeutic target","volume":"10","author":"Sorgdrager","year":"2019","journal-title":"Front. Immunol."},{"key":"ref48","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1385\/JMN:16:2-3:159","article-title":"Plasma free fatty acid and lipoproteins as sources of polyunsaturated fatty acid for the brain","volume":"16","author":"Spector","year":"2001","journal-title":"J. Mol. Neurosci."},{"key":"ref49","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1001\/archpsyc.1992.01820010029004","article-title":"Cerebrospinal fluid neurochemistry in children and adolescents with obsessive-compulsive disorder","volume":"49","author":"Swedo","year":"1992","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref50","doi-asserted-by":"publisher","first-page":"g2183","DOI":"10.1136\/bmj.g2183","article-title":"Obsessive-compulsive disorder","volume":"348","author":"Veale","year":"2014","journal-title":"BMJ"},{"key":"ref51","doi-asserted-by":"publisher","first-page":"822976","DOI":"10.3389\/fpsyt.2022.1046821","article-title":"Protocol for a pragmatic trial of pharmacotherapy options following unsatisfactory initial treatment in OCD (PROCEED)","volume":"13","author":"Wang","year":"2022","journal-title":"Front. Psych."},{"key":"ref52","doi-asserted-by":"publisher","first-page":"1819","DOI":"10.1152\/physrev.00035.2018","article-title":"Metabolomics for investigating physiological and pathophysiological processes","volume":"99","author":"Wishart","year":"2019","journal-title":"Physiol. Rev."},{"key":"ref53","doi-asserted-by":"publisher","first-page":"e100632","DOI":"10.1136\/gpsych-2021-100632","article-title":"The cost of obsessive-compulsive disorder (OCD) in China: a multi-center cross-sectional survey based on hospitals","volume":"34","author":"Yang","year":"2021","journal-title":"Gen Psychiatr."},{"key":"ref54","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1097\/YIC.0000000000000321","article-title":"5-Hydroxytryptophan as adjuvant therapy in treatment of moderate to severe obsessive-compulsive disorder: a double-blind randomized trial with placebo control","volume":"35","author":"Yousefzadeh","year":"2020","journal-title":"Int. Clin. Psychopharmacol."},{"key":"ref55","doi-asserted-by":"publisher","first-page":"92","DOI":"10.3109\/15622970009150571","article-title":"Obsessive compulsive disorder: serotonin and beyond","volume":"1","author":"Zohar","year":"2000","journal-title":"World J. Biol. Psychiatry"}],"container-title":["Frontiers in Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnins.2023.1148971\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,2]],"date-time":"2023-06-02T09:17:04Z","timestamp":1685697424000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnins.2023.1148971\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,2]]},"references-count":55,"alternative-id":["10.3389\/fnins.2023.1148971"],"URL":"https:\/\/doi.org\/10.3389\/fnins.2023.1148971","relation":{},"ISSN":["1662-453X"],"issn-type":[{"value":"1662-453X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,2]]},"article-number":"1148971"}}